SIALOADHESIN, MYELIN-ASSOCIATED GLYCOPROTEIN AND CD22 DEFINE A NEW FAMILY OF SIALIC ACID-DEPENDENT ADHESION MOLECULES OF THE IMMUNOGLOBULINSUPERFAMILY

Background: Protein-carbohydrate interactions are believed to be impor tant in many biological processes that involve cell-cell communication . Apart from the selectins, the only well-characterized vertebrate sia lic acid-dependent adhesion molecules are CD22 and sialoadhesin; CD22 is a member of the immunoglobulin superfamily that is expressed by B l ymphocytes and sialoadhesin is a macrophage receptor. The recent cloni ng of the gene encoding sialoadhesin has shown that it is also immunog lobulin-like. Both proteins share sequence similarity with the myelin- associated glycoprotein, an adhesion molecule of oligodendrocytes and Schwann cells that has been implicated in the process of myelination, raising the important question of whether myelin-associated glycoprote in is also a sialic acid-binding protein. Results: We have investigate d the binding properties oi these three receptors when expressed eithe r in monkey COS cells or as chimaeric proteins containing the Fc porti on of human immunoglobulin G. We demonstrate that, like sialoadhesin a nd CD22, myelin-associated glycoprotein mediates cell adhesion by bind ing to cell surface glycans that contain sialic acid. We have dissecte d the specifities of these three adhesins further: whereas sialoadhesi n binds equally to the sugar moieties NeuAc alpha 2 --> 3Gal beta 1 -- > 3(4)GlcNAc or NeuAc alpha 2 --> 3Gal beta 1 --> 3GalNAc, myelin-asso ciated glycoprotein recognizes only NeuAc alpha 2 --> 3Gal beta 1 --> 3GalNAc and CD22 binds specifically to NeuAc alpha 2 --> 6Gal beta 1 - -> 4GlcNAc. Furthermore, we show that the recognition of sialylated gl ycans on the surfaces of particular cell types leads to the selective binding of sialoadhesin to neutrophils, myelin-associated glycoprotein to neurons and CD22 to lymphocytes. Conclusions: Our findings demonst rate that a subgroup of the immunoglobulin superfamily can mediate div erse biological processes through recognition of specific sialylated g lycans on cell surfaces. We propose that this subgroup of proteins be called the sialoadhesin family.